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. Author manuscript; available in PMC: 2020 Jan 1.
Published in final edited form as: FEBS J. 2019 Jan;286(2):413–425. doi: 10.1111/febs.14739

Fig. 2. Role of ER stress in Darier’s disease.

Fig. 2.

In Darier’s disease, mutations in the ATP2A2 gene, which encodes the SERCA2, cause impaired transport of calcium from cytosol to ER, thereby leading to chronic ER stress in keratinocytes. ER calcium is an important regulator of the reorganization of adherens junctions and desmosomes. Defective ER calcium homeostasis in keratinocytes of Darier’s disease may contribute to abnormal cell-to-cell adhesion via defective reorganization of junctional components, causing acantholysis. In addition, chronic ER stress triggers the disproportionate activation of the apoptotic component of the UPR. PERK-dependent apoptotic signaling can contribute to the non-physiologic and premature keratinocyte apoptosis which can be observed as dyskeratotic keratinocytes (“corp ronds”) in Darier’s disease. Taken together, ER stress is implicated in the pathogenesis of Darier’s disease characterized histologically by acantholytic dyskeratosis.